A randomized, 5-arm dose finding study with a mite allergoid SCIT in allergic rhinoconjunctivitis patients
Por:
Pfaar, O, Nell, MJ, Boot, JD, Versteeg, SA, van Ree, R, Roger, A, Riechelmann, H, Sperl, A, Elberink, JNGO, Diamant, Z and Bachert, C
Publicada:
1 jul 2016
Resumen:
Background: The safety and tolerability of a mite allergoid subcutaneous allergen immunotherapy (SCIT) product was previously established. The aim of this study (EudraCT number: 2011-000393-61) was to find the optimally safe and effective allergoid dose by evaluating several dosages in patients with house dust mite (HDM)-induced allergic rhinoconjunctivitis (ARC) using a titrated nasal provocation test (TNPT).
Methods: In total, 290 adult ARC patients (148 females; 142 males) with established HDM allergy and with a positive TNPT were randomized to receive placebo or mite allergoid SCIT 6667, 20 000, 50 000 or 100 000 AUeq/ml for 12 months. Patients were updosed weekly, followed by monthly maintenance dosing. The primary study endpoint comprised the clinical response to TNPT after 12 months of treatment. Secondary endpoints included response to TNPT after 6 months, PNIF measurements, symptom and medication scores during the last 8 weeks of treatment, serum immunoglobulins and safety assessments.
Results: After 12 months, a dose-response was observed showing statistically significant improvements in the TNPT with SCIT concentrations of >= 20 000 AUeq/ml, while no significantly different outcomes were reached after 6 months. Specific serum IgG and IgG4 levels were dose dependently increased. In the highest dose group, more treatment-emergent adverse events were observed compared with the lower dose groups.
Conclusion: In this mite allergoid SCIT dose finding study in HDM-induced ARC, concentrations of >= 20 000 AUeq/ml showed both immunological effects and clinical efficacy in the TNPT compared with placebo. The risk-benefit ratio favours 20 000 AUeq/ml and 50 000 AUeq/ml strengths for further clinical development.
Filiaciones:
Pfaar, O:
Ctr Rhinol & Allergol, Wiesbaden, Germany
Heidelberg Univ, Dept Otorhinolaryngol Head & Neck Surg, Univ Med Mannheim, Med Fac Mannheim, Mannheim, Germany
Nell, MJ:
HAL Allergy BV, Leiden, Netherlands
Boot, JD:
HAL Allergy BV, Leiden, Netherlands
Versteeg, SA:
Univ Amsterdam, Acad Med Ctr, Expt Immunol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
van Ree, R:
Univ Amsterdam, Acad Med Ctr, Expt Immunol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
:
Hosp Badalona Germans Trias & Pujol, Unitat Allergia, Badalona, Spain
Riechelmann, H:
Med Univ Innsbruck, Dept Otorhinolaryngol Head & Neck Surg, A-6020 Innsbruck, Austria
Sperl, A:
Ctr Rhinol & Allergol, Wiesbaden, Germany
Elberink, JNGO:
Univ Groningen, Univ Med Ctr Groningen, Dept Allergol, Groningen, Netherlands
Diamant, Z:
Skane Univ Hosp, Dept Resp Med & Allergol, Inst Clin Sci, Lund, Sweden
Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands
Univ Groningen, Univ Med Ctr Groningen, Dept Gen Practice, Groningen, Netherlands
Bachert, C:
Univ Ghent, Upper Airways Res Lab, B-9000 Ghent, Belgium
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